scholarly journals Aberrant Transforming Growth Factor β1 Signaling and SMAD4 Nuclear Translocation Confer Epigenetic Repression of ADAM19 in Ovarian Cancer

Neoplasia ◽  
2008 ◽  
Vol 10 (9) ◽  
pp. 908-IN2 ◽  
Author(s):  
Michael W.Y. Chan ◽  
Yi-Wen Huang ◽  
Corinna Hartman-Frey ◽  
Chieh-Ti Kuo ◽  
Daniel Deatherage ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Transforming Growth Factor Β1 ◽  
Epigenetic Repression

scholarly journals Smad7 Abrogates Transforming Growth Factor-β1-mediated Growth Inhibition in COLO-357 Cells through Functional Inactivation of the Retinoblastoma Protein

2005 ◽  
Vol 280 (23) ◽  
pp. 21858-21866 ◽  
Author(s):  
Nichole Boyer Arnold ◽  
Murray Korc
Keyword(s):  
Growth Factor ◽  
Growth Inhibition ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Retinoblastoma Protein ◽  
Transforming Growth Factor Β1 ◽  
Type I ◽  
Pancreatic Cancer Cells ◽  
Induced Apoptosis ◽  
Tgf Β1

Smad7 is overexpressed in 50% of human pancreatic cancers. COLO-357 pancreatic cancer cells engineered to overexpress Smad7 are resistant to the actions of transforming growth factor-β1 (TGF-β1) with respect to growth inhibition and cisplatin-induced apoptosis but not with respect to modulation of gene expression. To delineate the mechanisms underlying these divergent consequences of Smad7 overexpression, we studied the effects of Smad7 on TGF-β1-dependent signaling pathways and cell cycle regulating proteins. TGF-β1 induced the phosphorylation of MAPK, p38 MAPK, and AKT2 irrespective of the levels of Smad7, and inhibitors of these pathways did not alter TGF-β1 actions on cell growth. By contrast, Smad7 overexpression interfered with TGF-β1-mediated attenuation of cyclin A and B levels, inhibition of cdc2 dephosphorylation and CDK2 inactivation, up-regulation of p27, and the maintenance of the retinoblastoma protein (RB) in a hypophosphorylated state. Smad7 also suppressed TGF-β1-mediated inhibition of E2F activity but did not alter TGF-β1-mediated phosphorylation of Smad2, the nuclear translocation of Smad2/3/4, or DNA binding of the Smad2/3/4 complex. Although Smad7 did not associate with the type I TGF-β receptor (TβRI), SB-431542, an inhibitor of the kinase activity of this receptor, blocked TGF-β1-mediated effects on Smad-2 phosphorylation. These findings point toward a novel paradigm whereby Smad7 acts to functionally inactivate RB and de-repress E2F without blocking the activation of TβRI and the nuclear translocation of Smad2/3, thereby allowing for TGF-β1 to exert effects in a cancer cell that is resistant to TGF-β1-mediated growth inhibition.

Abstract 230: Cartilage Intermediate Layer Protein-1 Attenuates Pressure Overload-induced Cardiac Fibrosis by Targeting Transforming Growth Factor-β1

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Li Li ◽  
Cheng-Lin Zhang ◽  
Dan Wu ◽  
Li-Ling Wu
Keyword(s):  
Growth Factor ◽  
Intermediate Layer ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Pressure Overload ◽  
Transforming Growth Factor Β1 ◽  
Tgf Β1

Background: Cartilage intermediate layer protein-1 (CILP-1), a monomeric extracellular matrix glycoprotein expressed mainly in the middle zones of articular cartilage, interacts directly with transforming growth factor-β1 (TGF-β1). Recent studies showed that CILP-1 was upregulated in the heart tissue following cardiac ischemia reperfusion injury. However, the role of CILP-1 in pathological cardiac remodeling is poorly defined. Aims: To explore the effect of CILP-1 on myocardial interstitial fibrosis and reveal the possible molecular mechanism. Methods and Results: We found that CILP-1 was mainly expressed in mouse cardiac fibroblasts (CFs) by using western blot analysis and immunofluorescence. Myocardial expression of CILP-1 was upregulated in mice subjected to transverse aortic constriction (TAC) for 2, 4, and 8 weeks. AAV-9-mediated delivery of CILP-1 into mice increased the binding of CILP-1 with TGF-β1, attenuated interstitial fibrosis, and improved cardiac function. In cultured adult mouse CFs, CILP-1 overexpression inhibited myofibroblast differentiation and expression of profibrotic molecules induced by TGF-β1. Furthermore, CILP-1 attenuated TGF-β1-induced Smad3 phosphorylation and nuclear translocation. Conclusions: CILP-1 alleviates pressure overload-induced cardiac fibrosis and dysfunction. CILP-1 exerts its anti-fibrotic effect through targeting TGF-β1 signaling. This study will offer a new therapeutic strategy for preventing and treating myocardial interstitial remodeling.

miR-30d Blocked Transforming Growth Factor β1–Induced Epithelial-Mesenchymal Transition by Targeting Snail in Ovarian Cancer Cells

2015 ◽  
Vol 25 (9) ◽  
pp. 1574-1581 ◽  
Author(s):  
Zhongxue Ye ◽  
Le Zhao ◽  
Jie Li ◽  
Wei Chen ◽  
Xu Li
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β1 ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Polymerase Chain ◽  
Tgf Β1

ObjectiveMicroRNAs (miRs) are essential regulators of gene expression by suppressing translation or causing degradation of target mRNA. Growing evidence sheds light on the crucial roles of miR dysregulation in cancer development and progression. In this study, we focused on the role of miR-30d in transforming growth factor β1 (TGF-β1)–initiated epithelial-mesenchymal transition (EMT) in ovarian cancer cells.MethodsTransforming growth factor β1 (10 ng/mL) was used to initiate EMT in SKOV3 and 3AO cells. The expression of miR-30 family members was determined by quantitative real-time polymerase chain reaction. Messenger RNA and protein levels of E-cadherin, N-cadherin, vimentin, and Snail were detected by quantitative real-time polymerase chain reaction and Western blot, respectively. Cell migration and invasion capacities were evaluated by Transwell chamber assay. Luciferase activity assay was performed to verify the direct inhibition of Snail by miR-30d.ResultsMiR-30b, MiR-30c, and MiR-30d were down-regulated during TGF-β1–induced EMT in SKOV3 and 3AO ovarian cancer cells. Restoration of miR-30d by miR-30d mimic reversed TGF-β1–induced EMT phenotypes including the morphological changes, expression pattern of molecular markers (E-cadherin, N-cadherin), and migratory and invasive capabilities in ovarian cancer cells. Furthermore, Snail was identified as the direct target of miR-30d.ConclusionsOur results revealed that miR-30d functioned as a suppressor of ovarian cancer progression by decreasing Snail expression and thus blocking TGF-β1–induced EMT process, suggesting the potentiality of miR-30d analogs to be used as therapeutics for ovarian cancer.

Quercetin enhances transforming growth factor β1, secretion by human ovarian cancer cells

1994 ◽  
Vol 57 (2) ◽  
pp. 211-215 ◽  
Author(s):  
Giovanni Scambia ◽  
Pierluigi Benedetti Panici ◽  
F. O. Ranelletti ◽  
G. Ferrandina ◽  
R. de Vincenzo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer
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